PROJECT SUMMARY/ABSTRACT Severe kidney disease accounts for 7% of all Medicare and Medicaid costs. The most cost-effective way to perform dialysis uses an arteriovenous fistula to connect to dialysis machines, but fistula use is limited by the malfunctions immediately following creation (maturation failure), which can render up to 70% of all created fistulas unusable. Ultrasound monitoring of the fistula after it has been created can avoid malfunction by detecting problems that can be fixed with minimally invasive outpatient procedures. Unfortunately, though ultrasound has been shown to reduce the failure rate to only 22%, the ultrasounds examinations used to detect these problems are very expensive because they can only be performed at specialized vascular laboratories by ultrasound specialists. Because of the significant expensive, ultrasound scans are not currently performed in the postoperative period. If ultrasound were less expensive and more accessible, it could be performed during the maturation phase and eliminate most early fistula failures, reducing in significant clinical benefit for patients and substantial cost savings. We have developed a dual-component ultrasound-based solution, EchoSure, that can be utilized anywhere and does not require expert ultrasonographers. Our system can be used to examine a fistula during routine clinic visits by the same medical assistants that check patient vitals. This means that ultrasound monitoring of a fistula in the first few weeks after fistula creation can be done for little additional cost. We have proven that EchoSure works in blood vessels. This study proposes to prove that the EchoSure system, when used in hemodialysis fistula monitoring in large animals and patients, can substantially reduce fistula failure at the maturation stage. In this Phase IIB proposal, we will (1) construct a flow phantom benchtop model for testing and refinement of the EchoSure system within the parameters of hemodialysis access, (2) demonstrate the precision and accuracy of the EchoSure system when used by inexpert personnel and compared to a formal Duplex examination performed by expert ultrasonographers (3) use a large animal model of arteriovenous fistulae to test the ability of EchoSure to predict fistula maturation, incipient thrombosis, or failure, and to compare those findings to standard Duplex ultrasonography, and (4) use the EchoSure system in human patients undergoing arteriovenous fistula creation to test the ability of EchoSure to predict maturation failure as early as the second postoperative week. OVERALL IMPACT: EchoSure will allow rapid and early detection of problems with arteriovenous fistulas before malfunction in the maturation stage. This will both improve the success rate of fistula maturation and therefore enable patients to receive dialysis via a fistula initially, rather than a catheter, which leads to a 23% reduction in annual costs per patient. Because of the disproportionate resources devoted to end stage renal disease, our proposal has the potential to profoundly decrease the morbidity of end stage renal disease in the United States and to decrease costs.